Time to Modify Ban on HIV Infected Organ Donors, Medical Societies Say

Weaver, Janelle

doi: 10.1097/01.NEP.0000411458.38631.98

HIV infection is no longer the death sentence it was in the early 1980s, thanks to the effectiveness and widespread use of highly active antiretroviral therapy (HAART). Mortality from HIV disease has not been one of the 15 leading causes of death in the United States since 1997, according to the National Center for Health Statistics.

Because these individuals are now living longer, they are at greater risk of developing non-HIV-related kidney diseases, such as those associated with diabetes or hypertension. Although HAART has slowed the progression of HIV-associated kidney disease over the past 15 years, the incidence of end-stage renal disease is increasing among HIV-infected individuals, who are seeking renal transplantation in greater numbers. These patients are more likely to die than are uninfected people on the waiting list.

Some of these deaths could be avoided by revising the National Organ Transplant Act (NOTA), which prohibits the use of organs from HIV-infected donors. This ban was put into effect in 1988, before people knew it would be possible to effectively control HIV disease with medication, said Robert S. Gaston, MD, Professor of Medicine at the University of Alabama at Birmingham and President of the American Society of Transplantation (AST).

“Over time, that has changed dramatically, and the restriction put into place by NOTA is based on medical information that is no longer state-of-the-art.”

In light of recent encouraging research findings on transplantation in HIV-infected individuals, medical societies have endorsed a modification of NOTA, and some are even approaching members of Congress in an attempt to introduce new legislation.

If successful, these efforts could lead to several hundred additional HIV-infected patients receiving transplants every year, shortening the waiting list for both infected and uninfected candidates.

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‘Patients Do Well’

This estimate comes from a study published in March 2011 by the American Journal of Transplantation (2011;11:1209-1217), which reported that there are about 500 to 600 deceased HIV-infected patients whose organs potentially could be used for transplantation in the United States each year. The researchers examined data from the Nationwide Inpatient Sample, the HIV Research Network, and the United Network for Organ Sharing (UNOS) to quantify the potential impact of lifting the ban imposed by NOTA.

“We have a profound organ shortage, and there is a potential source of organs that every day we're putting in the garbage because of an antiquated law that was written wisely at the time of the AIDS scare but now is no longer medically relevant,” said senior study author Dorry L. Segev, MD, PhD, Associate Professor of Surgery and of Epidemiology at Johns Hopkins University.

Organ donations from HIV-infected patients could represent a significant addition to the total collection of organs, said Mohamed G. Atta, MD, MPH, Associate Professor of Medicine at Johns Hopkins University and a member of the Nephrology Times Editorial Board. Currently, about 17,000 kidney transplants are performed per year in the United States.

“It's a great idea to increase the pool of donors and give the chance to HIV-infected individuals on dialysis with end-stage renal disease to receive these kidneys.”

Other recent studies have provided promising results in HIV-infected individuals who received a kidney transplant. In South Africa, where the use of dialysis is limited, four HIV-infected recipients of HIV-infected kidneys had good renal function, no need for dialysis, and no clinically significant graft rejection one year after transplantation (N Engl J Med 2010;362:2336-2337).

In the United States, a multicenter prospective trial of 150 HIV-infected recipients of uninfected kidneys revealed high survival rates—about 95% at one year and 88% at three years (N Engl J Med 2010;363:2004-2014). Graft survival rates were about 90% at one year and 74% at three years.

These rates fall between those reported for older kidney transplant recipients and all kidney transplant recipients, the investigators noted. Moreover, HIV infection remained well controlled in these patients, and there were few HIV-associated complications after transplantation.

“What's pretty clear is that patients generally speaking do well, so I think many of us have had very good experiences performing organ transplants on HIV-infected individuals,” said Emily A. Blumberg, MD, coauthor of the multicenter US study, as well as Professor of Medicine and Director of Transplant Infectious Diseases at the University of Pennsylvania.

“That has made many people in the US think about whether the law should be revised to allow carefully controlled investigations using carefully selected HIV-infected donors and recipients.”

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Societies on Board

In the wake of these recent studies, a joint policy statement supporting a modification of NOTA was issued by the American Society of Transplant Surgeons, AST, the Association of Organ Procurement Organizations, and UNOS.

“Our understanding of HIV has progressed significantly since 1988, and we believe that, in the modern era of HIV care, a universal ban on transplants from HIV-infected donors may no longer be justified,” the statement asserted. These organizations “recommend that this potential donor pool for HIV–positive recipients be explored in carefully designed research settings, with oversight of appropriate federal agencies.”

Last September, the Centers for Disease Control and Prevention revealed new proposed guidelines for reducing the risk of virus transmission through transplantation. The document included recommendations for further research to estimate the number of HIV-infected potential organ donors, to evaluate HIV screening tests, and to assess the risks and benefits of transplanting organs from HIV-infected individuals into HIV–infected recipients.

Two months later, the American Medical Association (AMA) voted during its semiannual policy-making meeting to support amending NOTA to enable clinical research on the safety and effectiveness of organ transplantation from HIV-infected individuals.

“With the improvement in transplant outcomes coupled with the management of HIV disease, we're in a different place than we have ever been in this country,” said AMA Board Member Ardis D. Hoven, MD, Professor of Medicine at the University of Kentucky and Medical Director of the Bluegrass Care Clinic in Lexington, KY.

Beyond raising awareness of the issue, the AMA is working with policy experts on Capitol Hill to formulate strategies for changing the federal law. “We need to look at the risks and benefits of organ transplantation in these patients,” she said.

AMA's position on this issue can be attributed in part to Dr. Segev's efforts. Early last year, he contacted the HIV Medicine Association (HIVMA), a policy and advocacy organization of HIV medical professionals, to devise strategies for amending the ban on transplantation between HIV-infected individuals. HIVMA assembled a coalition of about 20 medical societies and HIV/AIDS organizations that were willing to go on record in support of modifying NOTA.

In response to advice from congressional staff that they seek the endorsement of at least one nonspecialist medical society, Dr. Segev and HIVMA staff drafted a resolution and asked delegates from the society's sister organization, the Infectious Diseases Society of America, to introduce it during the AMA's November policy-making meeting.

Except for minor changes, this is the resolution that the AMA approved, said HIVMA Policy Officer Kimberly Crump, MA.

“Having the AMA listed as a supporter will help our advocacy efforts because it extends endorsement of the change beyond the specialty medical societies to one of the largest and best known generalist medical organizations.”

HIVMA staff members are now in the process of identifying and approaching various members of Congress, targeting relevant committees and members who have previously supported legislation to expand organ donation, with the goal of gathering cosponsors and introducing a new bill in the next congressional session.

“People have been receptive to the idea, but it's difficult to get them to focus on the issue,” Ms. Crump said.

Dr. Segev agreed.

“There seems to be a tremendous amount of support for this, but there's that barrier between support and action that we're trying to cross right now,” he said. “We're just now trying to find which members will take it one step further and consider it a priority for them. I'm very optimistic and hopeful that we'll be successful with this.”

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‘Nothing's Without Risk’

Despite the strong support for amending the National Organ Transplant Act and the potential benefits that could result from this action, HIV-infected organ donation also could come with several risks.

The multicenter US study of kidney transplantation in HIV-infected recipients showed two-to-three times higher-than-expected graft rejection rates in this patient population: 31% one year later and 41% three years later. In addition, 38% of these patients had infections that required hospitalization.

These findings underscore the need for future research to determine how to achieve an optimal balance between immunosuppressive and antiretroviral medications.

Another risk involves the accidental transplantation of an HIV-infected organ into an individual who was not infected with HIV before the procedure.

“There are always things like that that happen in medicine, but they're exceedingly rare, and I think that the likelihood of that happening would be so low as to not be a major consideration,” Dr. Gaston said.

The transplantation of organs infected with the hepatitis C virus serves as a precedent for preventing that type of mistake, Dr. Segev noted.

“We transplant hepatitis C-infected patients with hepatitis C-infected organs all of the time, and it's unheard of for somebody to accidentally receive the wrong organ.”

In addition to these concerns, transplant recipients could become infected with a slightly different version of the virus, causing their HIV disease to run rampant, Dr. Segev added.

“But there's a tremendous amount of knowledge about the various HIV types and the various treatments for these things, and most forms of HIV can be controlled with modern HAART,” he said.

“Obviously there are things to be learned, but there's not a profound concern that patients will die if they undergo transplantation. In fact, the concern is more that they will die if they don't.”

According to the United States Renal Data System, about two-thirds of patients undergoing dialysis die within five years, whereas about 9% to 19% of kidney transplant patients die during this time frame, depending on whether they received a living or deceased donor organ.

“Transplant is the treatment of choice for end-stage renal disease, regardless of whether the cause is HIV,” Dr. Atta said. “It would be economically good for the US health system because it would reduce the cost of dialysis, and it would be good for the patients because it would likely give them a much better quality of life and chance of survival compared with being on dialysis.”

To reduce the risks associated with transplantation, multidisciplinary teams that include HIV specialists would be necessary to ensure that potential donors have been compliant with taking antiretroviral medications, have suppressed viral loads, and do not have a resistant virus strain, Dr. Atta said.

These considerations are important because kidneys are a reservoir for HIV, and the immune system of transplant recipients may not be able to control viral replication in the donated kidney, especially since they take immunosuppressive drugs to prevent graft rejection, he explained.

“Nothing's without risk,” Dr. Atta said. “But if you give the choice to an HIV-infected individual on dialysis to take a kidney from another HIV–infected individual, my guess is that they will say yes.”

© 2012 Lippincott Williams & Wilkins, Inc.